Trends in Biotechnology

Governance strategies for biological AI: beyond the dual-use dilemma A common framing for governing artificial intelligence (AI) in the biological sciences is to focus on risk mitigation owing to the technology’s potential ‘dual-use’ for both beneficial and harmful applications. This is a reactive policy approach, and a broader framing that urges policymakers to actively champion the benefits alongside mitigating risks is needed, including through targeted investments aimed at securing public priorities.

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Small but mighty: emerging roles of uORFs in plants The discovery and manipulation of upstream open reading frames (uORFs) represent a promising frontier in plant biotechnology, offering strategies to enhance disease resistance and crop resilience. Here, we explore the role of uORFs in regulating gene expression under biotic stress and discuss approaches to engineer uORFs for sustainable agriculture and precision breeding.

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Bioinspired thermoreversible bioink orchestrates focal adhesion-dependent osteogenesis A bioinspired, multi-material bioprinting platform integrates a bone extracellular matrix–mimetic bioink with a load-bearing calcium phosphate phase, achieving mechanical strength 200× greater compared with conventional bioprints. By leveraging focal adhesion to orchestrate osteogenesis, this modular, bioresorbable platform bridges mechanical integrity and biological function for personalized, load-bearing bone reconstruction.

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How a kidney microenvironment atlas can advance kidney tissue engineering Despite advances in cellular knowledge through kidney cell and protein atlases, tissue-engineered kidney models remain functionally incomplete. A major gap lies in our limited knowledge of the extracellular matrix (ECM) and the mechanical properties of the kidney microenvironment – key factors that influence cell behavior, differentiation, and function. Current data, that are often based on animal models, lack human-specific, segment-level, and disease-related insights regarding the ECM and mechanical properties. To close this gap, we propose the development of a segment-specific Kidney Microenvironment Atlas: a comprehensive resource that details ECM composition, mechanical characteristics, disease-associated changes, interspecies differences, and measurement techniques. This atlas will inform the creation of more physiologically accurate in vitro models, and thus enhance disease modeling, drug testing, and future clinical applications.

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Emerging applications of carbon dots in plant (epi)genomics Carbon dots (CDs) have broad applications across life sciences. This forum highlights the most recent breakthroughs of CDs in plant genomics and epigenomics, including gene transcription, their roles as carriers for delivering DNA, RNA, and agrochemicals in gene expression/silencing, and their utility in genomic and epigenomic studies. Potential future directions are proposed.

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Nanobodies: a new frontier in plant disease management Nanobodies (Nbs) offer high potency, specificity, stability, and engineering versatility. Although well established in biomedicine, their use in crop protection is only emerging. In this forum, we summarize key advances in Nb-based immune receptors, antiviral and antifungal agents, and diagnostic tools, while discussing associated challenges and prospects in plant disease management.

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Microalgae-made biopharmaceuticals and their potential role in the One Health approach Biopharmaceuticals play a crucial role in the One Health approach by providing preventive and therapeutic solutions that support both human and animal health. The microalgae-based platform for producing biopharmaceuticals offers low production costs, benefiting both sectors, and thus represents a promising strategy to advance the One Health initiative. Over the past decade, significant progress has been made in genetic engineering and bioprocessing of algal systems; however, no microalgae-made biopharmaceuticals for human use have yet reached the market. This review provides an updated perspective on these advances and highlights future directions for the field, with a focus on overcoming the hurdles that have delayed the application of this technology.

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Rational bioengineering of polysaccharide in designing of microbiome modulation Targeted modulation of the gut microbiome offers significant promise for preventing and treating diverse diseases; yet, enhancing the efficacy of these interventions remains challenging. Polysaccharides have emerged as potent microbiome modulators, functioning as prebiotics that selectively promote beneficial bacterial growth and metabolite production. Their resistance to gastric degradation and selective intestinal fermentation enhance the precision of microbiome modulation while facilitating direct immunomodulatory interactions via pattern recognition receptor engagement on gut immune cells. Despite their high potential, polysaccharide-based microbiome modulators remain underrecognized. Advances in polysaccharide bioengineering now allow rational design of structure–function relationships, enabling targeted control of microbial communities and host immune responses. This review highlights these developments and applications, providing a timely perspective on next-generation microbiome-targeted strategies.

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Brown adipose tissue engineering: advances, challenges, and future directions Obesity is a major health issue as it increases the risk of developing chronic diseases, including cardiovascular disorders, diabetes, and certain types of cancer. Brown adipose tissue (BAT) is a promising target for obesity treatment due to its ability to burn fat and create heat via non-shivering thermogenesis. The development of BAT models for therapeutic use has become possible through recent advances in tissue engineering, including stem cell-based methods, 3D bioprinting, and organoid systems. However, optimizing differentiation protocols while maintaining the physiological relevance of BAT remains challenging. This review explores current advances in BAT engineering and highlights future research priorities for achieving clinical applications in metabolic health interventions.

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Plant genome editing goes viral: balancing innovation and biosafety Weiss and colleagues demonstrated a breakthrough in transgene-free heritable genome editing using viral vectors. While promising for controlled laboratory applications, the open-field use envisaged by Sajjad and colleagues raises ecological and biosafety concerns. Rigorous risk assessment is essential to harness innovation responsibly while safeguarding biodiversity and public trust.

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Virus-like particles as modular interfaces for biomaterial functionalization This study showcases virus-like particles (VLPs) as customizable nanoscale scaffolds for biomaterial surface functionalization. Using modified VLPs, we achieve high density display and confinement of bioactive peptides, offering a modular, animal-free, and cost-effective alternative to native extracellular matrix (ECM) proteins in tissue engineering and regenerative medicine.

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Staying productive under pressure: systems evaluations of β-carotene production in Yarrowia lipolytica under continuous fermentation This integrative experimental and modeling study explores how fermentation conditions affect β-carotene production in Yarrowia lipolytica. Oil-based feedstocks enhance stability in continuous fermentation compared with glucose, while high-yielding laboratory strains often falter in industrial bioreactors, where faster-growing but less productive variants dominate under stress and determine long-term outcomes.

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A practical guide to spatial transcriptomics: lessons from over 1000 samples Spatial transcriptomics (ST) enables the  in situ mapping of gene expression, revolutionizing our ability to study tissue organization and cellular interactions. However, many groups struggle with practical barriers to implementation, including platform selection, sample quality, and experimental scalability. We provide a practical guide to ST, informed by the processing and analysis of over 1000 spatial samples across multiple ST platforms. We outline best practices for experimental design, tissue handling, sequencing, and computational analysis, with special attention to clinical samples. Our goal is to translate hands-on experience into recommendations that support robust, reproducible spatial workflows. This guide is designed to assist researchers at all levels: from those designing their first spatial experiment to groups aiming to integrate ST into large-scale studies.

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Are amyloid-based materials conducive to tissue engineering? Amyloid fibrils, known for their stable, cross-β-sheet structure, are involved in both pathological conditions and functional biological processes. While implicated in disease pathogenesis, such as Alzheimer's and Parkinson’s, they also play roles in normal cellular functions, such as biofilm formation, melanin polymerization, and hormone storage. Amyloid-based biomaterials have gained attention for their stability, mechanical strength, unique surface properties, and structural versatility, making them suitable for various biotechnological applications. This review discusses their recent advancements and potential as biomaterials for tissue engineering, such as scaffolds for cell culture, wound healing, and organoid development. The unique properties of amyloids, combined with advances in structural and synthetic biology, position them as promising candidates for innovative biomaterials in medical and biotechnological fields.

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Viral genome editing: striking a balance between promises and precautions Viral vectors can provide transgene-free genome editing. The forward-looking frameworks for their use must be biosafety and freedom from ecological risk. The responsible innovations, showing a balance between promise and caution following regulatory frameworks, can guarantee that viral genome editing develops into a revolutionary but environmentally conscious strategy for sustainable agricultural improvement.

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Microbial tools and regulatory innovations for climate-resilient winemaking Climate-induced acidity loss threatens wine quality, prompting sustainable microbial acidification strategies using Lachancea thermotolerans. This yeast naturally reduces pH and ethanol, aligns with consumer preferences, and benefits from omics-driven selection and enabling policy frameworks. Adaptation requires coordinated biotechnological innovation, institutional backing, and clear consumer communication to maintain sustainability and competitiveness.

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Nanobotic microbiomes against emerging vascular pathogens in agriculture Vascular diseases in plants are exceptionally difficult to control. Escalating global climate change further increases the risks of outbreaks from existing and emerging pathogens. Nano-enabled microbiome engineering (NME) represents an innovative framework for targeted vascular plant pathogen control, offering a sustainable platform to enhance agricultural resilience and productivity.

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Online now: Towards scalable anammox: mechanistic insights and emerging strategies

The metabolic guide to space survival The Metabolic Guide to Space Survival (https://kristinapulejkova.com/the-metabolic-guide-to-space-survival/) is a multidisciplinary exploration of microbial life as a key to long-term survival in space. Framed through the voice of fictional character Chief Bioengineer Mira Kordan, the work unfolds across a speculative design toolkit, a narrative guidebook, and an architectural installation animated by holographic projections of Mira navigating life in zero gravity. The piece was created by London-based artist Kristina Pulejkova whose interdisciplinary work explores how the use of technology might lead to greater forms of sustainability in human-nature relationships.

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Semi-automated biofoundry workflows for sequence coevolution-guided isoprene synthase engineering We developed biofoundry workflows for efficient enzyme engineering, integrating a simple and accessible computational tool with automation to reduce time and resources. Using this approach, isoprene synthase was engineered for enhanced catalytic efficiency and thermostability, and also enhanced methane-to-isoprene conversion when applied to methanotrophs, highlighting its potential for methane-based biomanufacturing.

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Ethical and legal considerations of digital animal models: pioneering reduction and replacement The development of digital animal models represents a promising avenue for advancing the ethical principles of reduction and replacement in biomedical research. This paper discusses the potential of models built upon artificial intelligence (AI)-generated synthetic datasets simulating the characteristics and behaviors of model organisms, reducing reliance on live animals in research.

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Sustainable protection of multiple hosts against polyphagous pests using Plant Probiotic-Based Gene Silencing RNAi controls pests efficiently but faces limitations in managing polyphagous species due to insufficient persistence or narrow-spectrum plant protection. Plant Probiotic-based Gene Silencing uses engineered probiotics that can colonize various plants to deliver dsRNA, enabling sustainable protection of multiple host plants of polyphagous pests.

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Food production from air: gas precision fermentation with hydrogen-oxidising bacteria The breach of six planetary boundaries highlights the need for sustainable food production. Aerobic hydrogen-oxidising bacteria (HOBs) convert atmospheric CO2 and green hydrogen (H2) into biomass via gas fermentation, a process already used for food-grade single-cell protein production. This approach enables a supply chain independent of agriculture, requiring minimal land and water, with potential for carbon-neutral production and carbon capture. To expand beyond single-cell protein, HOBs must be engineered into cell factories for precision fermentation. Advances in synthetic biology, metabolic engineering, computational modelling, and bioreactor design have accelerated the development of scalable bioprocesses providing a blueprint for gas-based fermentation. We present a path forward using secreted recombinant milk protein as a case study, highlighting key challenges and opportunities.

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Making cow-free caseins and casein micelles A key step in the precision fermentation of casein proteins is correct phosphorylation to generate one or more short linear sequence motifs (SLiMs) containing three or more phosphorylated seryl residues. The work of Balasubramanian et al. takes us a step closer to that goal by showing that two bacterial phosphokinases are promising alternatives to the mammalian Golgi phosphokinases and casein kinase-II.

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Metabolic and immunomodulatory control of type 2 diabetes via generating cellular itaconate reservoirs by inflammatory-targeting gene-therapy nanovesicles NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3)+ macrophage accumulation in tissue promotes type 2 diabetes (T2D) progression. However, there is no precise, comprehensive, broad-spectrum inhibitor of the NLRP3 inflammasome for T2D therapy. We developed gene-therapy nanovesicles to regulate cellular itaconate production and mitochondrial function. This technology enables metabolic and immunomodulatory control of T2D.

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Flying seed-inspired sensors for remote environmental monitoring on Earth and beyond Exploring mobility beyond traditional robotic systems such as walking, swimming, and jumping, flight through dispersal, gliding, or hovering remains an untapped frontier for advanced stimulus-responsive and -sensing materials. Nature-inspired engineering has been a foundational aspect of robotic innovations, and biohybrid and biomimetic flying seeds are now becoming a significant example of this concept. By mimicking the aerodynamic properties and dispersal mechanisms of natural seeds, semi- and fully artificial systems are being designed for environmental monitoring, precision agriculture, and disease management applications that require wide-area coverage. Scientists are biomimicking these structures to explore the Martian surface and subsurface. This opinion article highlights the potential of flying seed-inspired sensors to advance environmental monitoring on Earth and planets such as Mars and beyond.

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Engineering chimeric signaling proteins for microbial whole-cell biosensors: from design to deployment Microbial whole-cell biosensors (MWCBs) harness living cells to detect analytes and produce measurable outputs, enabling continuous, low-cost, and in situ sensing. Central to MWCB function are modular sensing architectures, which can be reprogrammed to respond to diverse signals. Particularly, two-component systems (TCSs) and allosteric transcription factors (aTFs) offer modular, engineerable frameworks for building chimeric proteins. Recent advances in domain swapping, fusion point selection, and protein engineering are expanding the versatility and specificity of these systems, presenting new opportunities for tailored and multiplexed detection. However, translating chimeric MWCBs into real-world applications still faces multiple hurdles. This review examines current strategies for engineering TCS- and aTF-based biosensors and outlines key opportunities and challenges for their deployment in applications such as diagnostics, environmental monitoring, and biomanufacturing.

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Highly efficient prime editors for mammalian genome editing based on porcine retrovirus reverse transcriptase This study developed a highly efficient prime editing system (pvPE) based on porcine endogenous retroviral reverse transcriptase. Through extensive engineering and nocodazole treatment, pvPE achieved robust multigene editing in porcine fibroblasts, which generated Alzheimer’s disease pig models, offering a versatile platform for agricultural and biomedical applications.

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Engineering infrared light detection in blind human retina using ultrasensitive human TRPV1 channels We engineered a human transient receptor potential vanilloid 1 (TRPV1) variant the thermal threshold of which matches near-infrared microheating. Delivered by adeno-associated virus (AAV) to blind human retina, the novel single-component channel elicited robust, graded infrared responses without foreign proteins or nanoparticles, offering an opsin-free route to vision restoration and a platform for broader clinical-use thermal neuromodulation.

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Cell Symposia

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